The regulatory mechanism of physiological sleep-wake / 中国药理学通报

This paper explains the mechanism of the mutual switching between physiological sleep and wakefulness from the aspects of the sleep circadian system and the sleep homeostasis system. In the circadian rhythm system, with the suprachiasmatic nucleus as the core, the anatomical connections between the suprachiasmatic nucleusand various systems that affect sleep are summarized, starting from the suprachiasmatic nucleus, passing through the four pathways of the melatonin system, namely, subventricular area of the hypothalamus, the ventrolateral nucleus of the preoptic area, orexin neurons, and melatonin, then the related mechanisms of their regulation of sleep and wakefulness are expounded. In the sleep homeostasis system, with adenosine and prostaglandin D2 as targets, the role of hypnogen in sleep arousal mechanisms in regulation is also expounded.

Rudimentary horn pregnancy: clinical analysis of 12 cases and literature review / 中华妇产科杂志

Objective: To investigate the clinical characteristics, treatments and fertility recovery of rudimentary horn pregnancy (RHP). Methods: The clinical data of 12 cases with RHP diagnosed and treated in Peking University Third Hospital from January 1, 2010 to December 31, 2022 were retrospectively analyzed. Clinical informations, diagnosis and treatments of RHP and the pregnancy status after surgery were analyzed. Results: The median age of 12 RHP patients was 29 years (range: 24-37 years). Eight cases of pregnancy in residual horn of uterus occurred in type Ⅰ residual horn of uterus, 4 cases occurred in type Ⅱ residual horn of uterus; among which 5 cases were misdiagnosed by ultrasound before surgery. All patients underwent excision of residual horn of uterus and affected salpingectomy. After surgery, 9 patients expected future pregnancy, and 3 cases of natural pregnancy, 2 cases of successful pregnancy through assisted reproductive technology. Four pregnancies resulted in live birth with cesarean section, and 1 case resulted in spontaneous abortion during the first trimester of pregnancy. No uterine rupture or ectopic pregnancy occurred in subsequent pregnancies. Conclusions: Ultrasonography could aid early diagnosis of RHP while misdiagnosis occurred in certain cases. Thus, a comprehensive judgment and decision ought to be made based on medical history, physical examination and assisted examination. Surgical exploration is necessary for diagnosis and treatment of RHP. For infertile patients, assisted reproductive technology should be applied when necessary. Caution to prevent the occurrence of pregnancy complications such as uterine rupture, and application of cesarean section to terminate pregnancy are recommended.

Expert Consensus on Clinical Diseases Responding Specifically to Traditional Chinese Medicine： Threatened Abortion / 中国实验方剂学杂志

Threatened abortion is a common disease of obstetrics and gynecology and one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in TCM obstetrics and gynecology， Western medicine obstetrics and gynecology， and pharmacology to deeply discuss the advantages of TCM and integrated Chinese and Western medicine treatment as well as the medication plans for threatened abortion. After discussion， the experts concluded that chromosome， endocrine， and immune abnormalities were the key factors for the occurrence of threatened abortion， and the Qi and blood disorders in thoroughfare and conception vessels were the core pathogenesis. In the treatment of threatened abortion， TCM has advantages in preventing miscarriages， alleviating clinical symptoms and TCM syndromes， relieving anxiety， regulating reproductive endocrine and immune abnormalities， personalized and diversified treatment， enhancing efficiency and reducing toxicity， and preventing the disease before occurrence. The difficulty in diagnosis and treatment of threatened abortion with traditional Chinese and Western medicine lies in identifying the predictors of abortion caused by maternal factors and the treatment of thrombophilia. Recurrent abortion is the breakthrough point of treatment with integrated traditional Chinese and Western medicine. It is urgent to carry out high-quality evidence-based medicine research in the future to improve the modern diagnosis and treatment of threatened abortion with TCM.

Synthesis and antibacterial activity evaluation of octapeptin derivatives / 药学学报

Octapeptin has strong antibacterial activity against Gram-negative bacteria such as Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii, while it also has activity against some Gram-positive bacteria. This study used natural octapeptin A3 and B3 as lead compounds for structural modification. Twenty-one peptide derivatives (including A3 and B3) containing eight amino acid residues were prepared by solid-phase synthesis, and evaluated for antibacterial activity and renal cytotoxicity. Among them, three compounds 6, 7 and 17 exhibited broad-spectrum antibacterial activity and significantly enhanced the activity for Gram-positive bacteria while maintaining the activity of Gram-negative bacteria. Several compounds improved the activity for Pseudomonas aeruginosa. Compound 7 was active against all test strains and had relatively low renal cytotoxicity. The results provide a basis for the further development of novel polypeptide antibiotics.

Evaluation of macular microvasculature alterations in patients with proliferative diabetic retinopathy after vitrectomy by swept-source optical coherence tomography angiography / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the changes in retinal and choroidal blood flow after pars plana vitrectomy(PPV)for proliferative diabetic retinopathy(PDR).METHODS: A cross-sectional study was conducted on 35 patients(35 eyes)who were diagnosed as monocular PDR and received 23GPPV in ophthalmology department of the Second People's Hospital of Hefei between September 2020 and July 2022. All eyes underwent swept-source optical coherence tomography angiography(SS-OCTA)examination. Retinal and choroidal vascular parameters within 3mm×3mm of macular zone were measured by built-in analyzer, and its correlation with postoperative best corrected visual acuity(BCVA)was analyzed.RESULTS: The follow-up was 1～22(average 9.72±6.67)mo. At the last follow-up, flow area(FA)of intermediate capillary plexus(ICP)layer in paranasal foveal region was significantly reduced in PPV eyes(0.31±0.06mm2)compared with contralateral eyes(0.38±0.05mm2), and FA of deep capillary plexus(DCP)in temporal foveal region was significantly lower in PPV eyes(0.19±0.08mm2)than contralateral eyes(0.27±0.07mm2; all P<0.05). Choroidal vascularity index(CVI)were lower in PPV eyes than contralateral eyes in parafoveal subregions except temporal region(P<0.05). After PPV, BCVA had a certain correlation with the density and FA of middle and deep retinal vessels.CONCLUSIONS: Eyes with severe PDR may be prone to having a decrease in the DCP and parafoveal choroidal perfusion in the parafoveal regions after PPV than contralateral eyes.

Huangqi Decoction, a compound Chinese herbal medicine, inhibits the proliferation and activation of hepatic stellate cells by regulating the long noncoding RNA-C18orf26-1/microRNA-663a/transforming growth factor-β axis / 中西医结合学报

OBJECTIVE@#Huangqi Decoction (HQD), a classical traditional Chinese medicine formula, has been used as a valid treatment for alleviating liver fibrosis; however, the underlying molecular mechanism is still unknown. Although our previous studies showed that microRNA-663a (miR-663a) suppresses the proliferation and activation of hepatic stellate cells (HSCs) and the transforming growth factor-β/small mothers against decapentaplegic (TGF-β/Smad) pathway, whether long noncoding RNAs (lncRNAs) are involved in HSC activation via the miR-663a/TGF-β/Smad signaling pathway has not yet reported. The present study aimed to investigate the roles of lncRNA lnc-C18orf26-1 in the activation of HSCs and the mechanism by which HQD inhibits hepatic fibrosis.@*METHODS@#The expression levels of lnc-C18orf26-1, miR-663a and related genes were measured by quantitative reverse transcription-polymerase chain reaction. HSCs were transfected with the miR-663a mimic or inhibitor and lnc-C18orf26-1 small interfering RNAs. The water-soluble tetrazolium salt-1 assay was used to assess the proliferation rate of HSCs. Changes in lncRNA expression were evaluated in miR-663a-overexpressing HSCs by using microarray to identify miR-663a-regulated lncRNAs. RNA hybrid was used to predict the potential miR-663a binding sites on lncRNAs. Luciferase reporter assays further confirmed the interaction between miR-663a and the lncRNA. The expression levels of collagen α-2(I) chain (COL1A2), α-smooth muscle actin (α-SMA) and TGF-β/Smad signaling pathway-related proteins were determined using Western blotting.@*RESULTS@#Lnc-C18orf26-1 was upregulated in TGF-β1-activated HSCs and competitively bound to miR-663a. Knockdown of lnc-C18orf26-1 inhibited HSC proliferation and activation, downregulated TGF-β1-stimulated α-SMA and COL1A2 expression, and inhibited the TGF-β1/Smad signaling pathway. HQD suppressed the proliferation and activation of HSCs. HQD increased miR-663a expression and decreased lnc-C18orf26-1 expression in HSCs. Further studies showed that HQD inhibited the expression of COL1A2, α-SMA, TGF-β1, TGF-β type I receptor (TGF-βRI) and phosphorylated Smad2 (p-Smad2) in HSCs, and these effects were reversed by miR-663a inhibitor treatment.@*CONCLUSION@#Our study identified lnc-C18orf26-1 and miR-663a as promising therapeutic targets for hepatic fibrosis. HQD inhibits HSC proliferation and activation at least partially by regulating the lnc-C18orf26-1/miR-663a/TGF-β1/TGF-βRI/p-Smad2 axis.

Correlation analysis of vitamin D level and anti-Müllerian hormone in infertile female and the role in predicting pregnancy outcome / 北京大学学报(医学版)

OBJECTIVE@#To investigate the relationship between serum 25(OH)D and anti-Müllerian hormone (AMH) among infertile females and their predictive impacts on in vitro fertilization and embryo transfer pregnancy outcome.@*METHODS@#Totally 756 infertile females treated with assisted reproductive technology were enrolled and divided into three groups according to their vitamin D levels (group A with serum 25(OH)D≤10 μg/L, group B with serum (10-20) μg/L, and group C with serum ≥20 μg/L). The serum AMH levels were detected. The differences among the groups were analyzed, as well as the correlation between vitamin D levels and serum AMH levels in various infertility types (fallopian tube/male factor, polycystic ovary syndrome (PCOS), ovulation disorders excluded PCOS, endometriosis, unexplained infertility, and others). Also, the predictive roles of vitamin D and AMH in pregnancy outcome in all the infertile females were discussed.@*RESULTS@#(1) 87.7% of the enrolled females were insufficient or deficient in vitamin D. (2) The serum AMH levels in the three groups with different vitamin D levels were 1.960 (1.155, 3.655) μg/L, 2.455 (1.370, 4.403) μg/L, 2.360 (1.430, 4.780) μg/L and there was no significant difference in serum AMH levels among the three groups (P>0.05). (3) Serum 25(OH)D and AMH levels presented seasonal variations (P < 0.05). (4) There was no prominent correlation between the serum AMH level and serum 25(OH)D level in females of various infertility types after adjusting potential confounding factors [age, body mass index (BMI), antral follicle count (AFC), vitamin D blood collection season, etc.] by multiple linear regression analysis (P>0.05). (5) After adjusting for confounding factors, such as age, BMI, number of transplanted embryos and AFC, the results of binary Logistics regression model showed that in all the infertile females, the serum AMH level was an independent predictor of biochemical pregnancy outcome (P < 0.05) while the serum 25(OH)D level might not act as a prediction factor alone (P>0.05). In the meanwhile, the serum 25(OH)D level and serum AMH level were synergistic predictors of biochemical or clinical pregnancy outcome (P < 0.05).@*CONCLUSION@#Based on the current diagnostic criteria, most infertile females had vitamin D insufficiency or deficiency, but there was not significant correlation between serum 25(OH)D and ovarian reserve. While vitamin D could not be used as an independent predictor of pregnancy outcome in infertile females, the serum AMH level could predict biochemical pregnancy outcome independently or jointly with vitamin D.

Effect of jejunal feeding tube placement on complications after laparoscopic radical surgery in patients with incomplete pyloric obstruction by gastric antrum cancer / 中华胃肠外科杂志

Objective: To assess the effect of jejunal feeding tube placement on early complications of laparoscopic radical gastrectomy in patients with incomplete pyloric obstruction by gastric cancer. Methods: This was a retrospective cohort study. Perioperative clinical data of 151 patients with gastric antrum cancer complicated by incomplete pyloric obstruction who had undergone laparoscopic distal radical gastrectomy from May 2020 to May 2022 in the First Affiliated Hospital of Nanchang University were collected. Intraoperative jejunal feeding tubes had been inserted in 69 patients (nutrition tube group) and not in the remaining 82 patients (conventional group). There were no statistically significant differences in baseline characteristics between the two groups (all P>0.05). The operating time, intraoperative bleeding, time to first intake of solid food, time to passing first flatus, time to drainage tube removal, and postoperative hospital stay, and early postoperative complications (occurded within 30 days after surgery) were compared between the two groups. Results: Patients in both groups completed the surgery successfully and there were no deaths in the perioperative period. The operative time was longer in the nutritional tube group than in the conventional group [(209.2±4.7) minutes vs. (188.5±5.7) minutes, t=2.737, P=0.007], whereas the time to first postoperative intake of food [(2.7±0.1) days vs. (4.1±0.4) days, t=3.535, P<0.001], time to passing first flatus [(2.3±0.1) days vs. (2.8±0.1) days, t=3.999, P<0.001], time to drainage tube removal [(6.3±0.2) days vs. (6.9±0.2) days, t=2.123, P=0.035], and postoperative hospital stay [(7.8±0.2) days vs. (9.7±0.5) days, t=3.282, P=0.001] were shorter in the nutritional tube group than in the conventional group. There was no significant difference between the two groups in intraoperative bleeding [(101.1±9.0) mL vs. (111.4±8.7) mL, t=0.826, P=0.410]. The overall incidence of short-term postoperative complications was 16.6% (25/151). Postoperative complications did not differ significantly between the two groups (all P>0.05). Conclusion: It is safe and feasible to insert a jejunal feeding tube in patients with incomplete outlet obstruction by gastric antrum cancer during laparoscopic radical gastrectomy. Such tubes confer some advantages in postoperative recovery.

Identification of risk genes in Chinese nonobstructive azoospermia patients based on whole-exome sequencing / 亚洲男科学杂志(英文版)

Nonobstructive azoospermia (NOA) is a severe condition in infertile men, and increasing numbers of causative genes have been identified during the last few decades. Although certain causative genes can explain the presence of NOA in some patients, a proportion of NOA patients remain to be addressed. This study aimed to investigate potential high-risk genes associated with spermatogenesis in idiopathic NOA patients by whole-exome sequencing. Whole-exome sequencing was performed in 46 male patients diagnosed with NOA. First, screening was performed for 119 genes known to be related to male infertility. Next, further screening was performed to determine potential high-risk causative genes for NOA by comparisons with 68 healthy male controls. Finally, risk genes with high/specific expression in the testes were selected and their expression fluctuations during spermatogenesis were graphed. The frequency of cystic fibrosis transmembrane conductance regulator (CFTR) gene pathogenic variant carriers was higher in the NOA patients compared with the healthy controls. Potential risk genes that may be causes of NOA were identified, including seven genes that were highly/specifically expressed in the testes. Four risk genes previously reported to be involved in spermatogenesis (MutS homolog 5 [MSH5], cilia- and flagella-associated protein 54 [CFAP54], MAP7 domain containing 3 [MAP7D3], and coiled-coil domain containing 33 [CCDC33]) and three novel risk genes (coiled-coil domain containing 168 [CCDC168], chromosome 16 open reading frame 96 [C16orf96], and serine protease 48 [PRSS48]) were identified to be highly or specifically expressed in the testes and significantly different in the 46 NOA patients compared with 68 healthy controls. This study on clinical NOA patients provides further evidence for the four previously reported risk genes. The present findings pave the way for further functional investigations and provide candidate risk genes for genetic diagnosis of NOA.

Mechanism of Liuwei Dihuang Pills in treatment of mice with diminished ovarian reserve based on proteomics / 中国中药杂志

This study aims to investigate the efficacy and possible mechanism of Liuwei Dihuang Pills in the treatment of diminished ovarian reserve(DOR) by using proteomic techniques. Firstly, cyclophosphamide(60 mg·kg~(-1)) combined with busulfan(6 mg·kg~(-1)) was injected intraperitoneally to establish the mouse model of DOR. After drug injection, the mice were continuously observed and the success of modeling was evaluated by the disturbance of the estrous cycle. After successful modeling, the mice were administrated with the suspension of Liuwei Dihuang Pills by gavage for 28 days. At the end of the gavage, four female mice were selected and caged together with males at a ratio of 2∶1 for the determination of the pregnancy rate. Blood and ovary samples were collected from the remaining mice on the next day after the end of gavage. Hematoxylin-eosin(HE) staining and transmission electron microscopy(TEM) were then employed to observe the morphological and ultrastructural changes in the ovaries. The serum levels of hormones and oxidation indicators were measured by enzyme-linked immunosorbent assay. Quantitative proteomics techniques were used to compare the ovarian protein expression before and after modeling and before and after the intervention with Liuwei Dihuang Pills. The results showed that Liuwei Dihuang Pills regulated the estrous cycle of DOR mice, elevated the serum levels of hormones and anti-oxidation indicators, promoted follicle development, protected the mitochondrial morphology of ovarian granulosa cells, and increased the litter size and survival of DOR mice. Furthermore, Liuwei Dihuang Pills negatively regulated the expression of 12 differentially expressed proteins associated with DOR, which were mainly involved in lipid catabolism, inflammatory response, immune regulation, and coenzyme biosynthesis. These differentially expressed proteins were significantly enriched in sphingolipid metabolism, arachidonic acid metabolism, ribosomes, ferroptosis, and cGMP-PKG signaling pathway. In summary, the occurrence of DOR and the treatment of DOR with Liuwei Dihuang Pills are associated with multiple biological pathways, mainly including oxidative stress response, inflammatory response, and immune regulation. "Mitochondria-oxidative stress-apoptosis" is the key to the treatment of DOR by Liuwei Dihuang Pills. YY1 and CYP4F3 may be the key upstream targets that trigger mitochondrial dysfunction and ROS accumulation, and the metabolism of arachidonic acid is the main signaling pathway of drug action.

Quantitative assessment of choriocapillaris perfusion in patients with diabetic retinopathy using ultra-high-speed swept source optical coherence tomography angiography / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the characteristics of choriocapillary blood flow in different patients with diabetic retinopathy(DR)based on the measurement of choriocapillaris(CC)perfusion density(PFD)using ultra-high-speed swept-source optical coherence tomography angiography(SS-OCTA)METHODS: The cross-sectional observational study was conducted on 139 cases(139 eyes)who admitted to the Second People's Hospital of Hefei, including 115 DR cases(115 eyes)and 24 control cases(24 eyes). The color retinal images were graded according to the Early Treatment Diabetic Retinopathy Study(ETDRS)scale, and the DR eyes were classified into non-DR group, nonproliferative diabetic retinopathy(NPDR)group, NPDR combined with diabetic macular edema(DME)group and proliferative diabetic retinopathy(PDR)group. The ultra-high-speed SS-OCTA was used to scan a 3mm×3mm region centered on the macular central fovea, the CC perfusion area was measured by the built-in software, and PFD was calculated. Multivariable linear regressions were used to evaluate the correlation between PFD of CC and DR degree.RESULTS: The degree of DR had a correlation with blood perfusion of CC after adjusting for various confounding factors. When compared to the control group, the PFD of CC in the central fovea of the NPDR group decreased by 9.358 units(95%CI -18.484～-0.232, P=0.045)and 9.284 units in the paracentral fovea(95%CI -18.487～-0.090, P=0.048); In the NPDR combined with DME group, the central fovea CC PFD decreased by 18.173 units(95%CI -28.583～-7.762, P=0.001), while the paracentral fovea decreased by 17.032 units(95%CI -27.521～-6.544, P=0.002); In the PDR group, the central fovea CC PFD decreased by 28.309 units(95%CI -39.978～-16.640, P&#x003C;0.001), while the paracentral fovea decreased by 25.841 units(95%CI -37.597～-14.085, P&#x003C;0.001).CONCLUSION: The macular perfusion can be objectively quantified by the measurement of CC PFD with ultra-high-speed SS-OCTA. The CC PFD in the macular region was significantly reduced in more advanced stages of DR. Furthermore, future research should focus on longitudinal studies in the causal relationship between CC perfusion and DR progression.

Vitreous properties in patients with diabetes mellitus and its relationship with proliferative diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

When it comes to diabetic patients, persistent hyperglycemia and associated pathological conditions will not only cause diabetic retinopathy(DR)but also have an impact on the metabolism of vitreous, leading to diabetic vitreopathy. Owing to the adjacent anatomical position between the vitreous and retina, diabetic vitreopathy and DR are mutually promoted. Changes in vitreoretinal interface such as posterior vitreous detachment(PVD)and vitreoschisis, provide a scaffold for fibrovascular proliferative membrane and are closely associated with pars plana vitrectomy(PPV). This article sorts out the variation of diabetic patients' vitreous structure and biochemical components, along with the changes in the vitreous-retinal interface, particularly for the related research on its relationship with proliferative diabetic retinopathy(PDR), aiming at providing further cognition of diabetic vitreopathy as well as references for DR treatment and formulation of PPV.

Efficacy of hepatic arterial infusion chemotherapy and its multimodality therapeutic regimens in treatment of patients with advanced hepatocellular carcinoma and related prognostic factors / 临床肝胆病杂志

Objective To investigate the efficacy of continuous hepatic arterial infusion chemotherapy (HAIC) with the FOLFOX regimen and its multimodality therapeutic regimen in the treatment of patients with advanced hepatocellular carcinoma, as well as the influencing factors for prognosis. Methods A retrospective analysis was performed for the clinical data of 66 patients with advanced hepatocellular carcinoma who received continuous HAIC with FOLFOX regimen in Nanfang Hospital, Southern Medical University, from September 2018 to November 2021. The patients were observed in terms of objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), and median overall survival (mOS) after treatment, and treatment-related adverse reactions were recorded. For the patients with portal vein tumor thrombus, the effect of the treatment on portal vein tumor thrombus was assessed. The Kaplan-Meier method was used for survival analysis, and the Cox regression analysis was used to investigate the influencing factors for prognosis. Results According to the RECIST1.1 criteria, FOLFOX-HAIC and its multimodality therapeutic regimen achieved an ORR of 33.3% (22/66) and a DCR of 86.4% (57/66) in the treatment of 66 patients with advanced hepatocellular carcinoma, with an mPFS time of 8.2 months and an mOS time of 22.1 months. Among the 39 patients with portal vein tumor thrombus, 2 achieved complete remission, 8 achieved partial remission, 24 achieved stable disease, and 5 had disease progression, with an ORR of 25.6% (10/39) and a DCR of 87.2% (34/39). The main adverse reactions included gastrointestinal reactions (16.7%, 11/66), pyrexia (12.1%, 8/66), liver area pain (10.6%, 7/66), bone marrow suppression (3.0%, 2/66), and contrast agent allergy (3.0%, 2/66), and there were no grade > Ⅳ toxic or side effects or deaths caused by such complications. The Cox regression analysis showed that extrahepatic metastasis (hazard ratio [ HR ]=2.668, 95% confidence interval [ CI ]: 1.357-5.245, P < 0.05) and prothrombin time (PT) ( HR =1.282, 95% CI : 1.080-1.630, P < 0.05) were independent risk factors for PFS, and aspartate aminotransferase level ( HR =1.008, 95% CI : 1.002-1.013, P < 0.05) and PT ( HR =1.303, 95% CI : 1.046-1.630, P < 0.05) were independent risk factors for OS. Conclusion FOLFOX-HAIC and its multimodality therapeutic regimen has a certain clinical effect with controllable adverse reactions in the treatment of advanced hepatocellular carcinoma.

Effect and mechanism of gerbeloid J from Gerbera piloselloides (L.) Cass. on cycle and apoptosis of breast cancer cells / 药学学报

Breast cancer has become the most prevalent malignant tumor among women, putting the health of women at serious risk. Screening for lead compounds in the active ingredients of plant that are effective and less toxic continues to be an important strategy for treating breast cancer. Gerbeloid J, a coumarin isolated from Gerbera piloselloides (L.) Cass., showed significant anti-cancer activity. But there is no report on the effect and mechanism of gerbeloid J on cycle and apoptosis of breast cancer. By using the CCK-8, clone formation, and PI staining assays, the effects of gerbeloid J on the proliferation of MCF-7 and MDA-MB-231 cells were assessed in this study. The effects of gerbeloid J on the apoptosis and mitochondrial function of MCF-7 and MDA-MB-231 cells were assessed using DAPI, Annexin V/TO-PRO-3, Rhod-2 AM, TMRM, DCFDA staining assays, and Western blot. The results demonstrated that gerbeloid J regulated the P21/CDC25C/CDK-1/cyclin B1 pathway and arrested the cell cycle at G2/M phase to suppressed the proliferation of MCF-7 and MDA-MB-231 cells. Additionally, gerbeloid J induced apoptosis through the stimulation of mitochondrial calcium excess, reduction of mitochondrial membrane potential, and promotion of ROS generation, and its mechanism was related to the activation of mitochondrial apoptotic pathway. In conclusion, by regulating the P21/CDC25C/CDK-1/cyclin B1 pathway and activating the mitochondrial apoptosis pathway, gerbeloid J could cause breast cancer cell cycle arrest and apoptosis, which might offer a promising candidate for the creation of new drugs against breast cancer.

Comparative analysis of clinical diagnosis and treatment guidelines for drug-induced liver injury at home and abroad / 中华肝脏病杂志

Drug-induced liver injury influencing factors are complex and have diverse clinical manifestations. Simple and reliable diagnostic methods are still deficient, and further classification of toxicological mechanisms is required. There are numerous pertinent discrepancies between domestic and international guidelines aimed at drug-induced liver injury diagnosis and treatment, with partial to no consensus on the content. The American Gastroenterological Association's 2021 Clinical Guidelines, the Asia-Pacific Association for the Study of the Liver's 2021 Consensus Guidelines, the Council for International Organizations of Medical Sciences' 2020 International Consensus, the European Society's Hepatology Committee's 2019 Clinical Practice Guidelines, and the 2015 Chinese Medical Association Guidelines are five influential clinical guidelines on drug-induced liver injury at home and abroad. The epidemiology, risk factors, diagnosis and evaluation, treatment management, and other contents, particularly traditional Chinese medicine, were compared and analyzed using other relevant consensus opinions or guidelines in order to improve understanding and provide a reference for clinical diagnosis and treatment of drug-induced liver injury.

Effect and safety of 10-day decitabine-containing conditioning regimen for allogeneic hematopoietic stem cell transplantation in 31 patients with acute myeloid leukemia/myelodysplastic syndrome / 中华血液学杂志

Objective: To investigate the early effect and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a 10-day decitabine-containing conditioning regimen in the treatment of acute myeloid leukemia (AML) /myelodysplastic syndrome (MDS) . Methods: From April 2021 to May 2022, 31 AML/MDS patients who received allo-HSCT with a 10-day decitabine-containing conditioning regimen were analyzed. Results: AML (n=10), MDS-AML (n=6), CMML-AML (n=1), and MDS (n=14) were identified in 31 patients, 16 males, and 15 females, with a median age of 41 (20-55) yr. Neutrophils and platelets were successfully implanted in 31 patients (100%), with a median implantation duration of 12 (9-30) and 14 (9-42) days, respectively. During the preconditioning period, 16 patients (51.6%) developed oral mucositis, with 15 cases of Ⅰ/Ⅱ grade (48.4%) and one case of Ⅲ grade (3.2%). After transplantation, 13 patients (41.9%) developed CMV viremia, six patients (19.4%) developed hemorrhagic cystitis, and four patients (12.9%) developed a local infection. The median time of acute graft versus host disease (aGVHD) following transplantation was 33 (12-111) days. The cumulative incidence of aGVHD and Ⅲ/Ⅳ grade aGVHD was 41.9% (95% CI 26.9%-61.0%) and 22.9% (95% CI 13.5%-47.5%), respectively. There was no severe cGVHD, and mild and moderate chronic GVHD (cGVHD) incidence was 23.5% (95% CI 12.1%-43.6%). As of November 30, 2022, only one of the 31 patients had relapsed, with a 1-yr cumulative relapse rate (CIR) of 3.2% (95% CI 0.5%-20.7%). There was only one relapse patient death and no non-relapse deaths. The 1-yr overall survival (OS) and disease-free survival (DFS) rates were 92.9% (95% CI 80.3%-100%) and 96.8% (95% CI 90.8%-100%), respectively. Conclusions: A 10-day decitabine-containing conditioning regimen for allo-HSCT reduced relapse and was safe and feasible in treating AML/MDS.

Report on Cardiac Gross Pathologic Measurements of Sudden Cardiac Death in Adults / 法医学杂志

OBJECTIVES@#To analyze the gross pathological data of sudden cardiac death (SCD) with different causes, to provide data support for the identification of sudden cardiac death with unknown causes.@*METHODS@#A total of 167 adult SCD cases in the archive of the Forensic Expertise Institute of Nanjing Medical University from 2010 to 2020 were collected. The gross pathological data of SCD cases were summarized and the characteristics of different causes of death were statistically analyzed.@*RESULTS@#The ratio of male to female SCD cases was 3.4∶1. Coronary heart disease was the leading cause of SCD, and mainly distributed in people over 40 years old. SCD caused by myocarditis was mainly distributed in young people and the mean age of death was (34.00±9.55) years. By analyzing the differences in cardiac pathological parameters of SCD with different causes, it was found that the aortic valve circumference was significantly dilated in the SCD caused by aortic aneurysm or dissection (P<0.05). The heart weight of SCD caused by aortic aneurysm or dissection and combined factors was greater, and both pulmonary and tricuspid valvular rings were dilated in the SCD caused by combined factors in adult males (P<0.05).@*CONCLUSIONS@#Various gross pathological measures of SCD with different causes are different, which has reference value in the cause of death identification of SCD.

Role of Adverse Events Supervision in Clinical Trials in Neoadjuvant Treatment of Operable Stage III NSCLC / 中国肺癌杂志

BACKGROUND@#Programmed cell death protein 1 (PD-1) combined with platinum containing dual drug chemotherapy is a new adjuvant treatment option for operable stage III non-small cell lung cancer (NSCLC), and the quality assurance of clinical trials of related drugs plays a crucial role in the results of the clinical trials. This study aims to explore the impact of adverse events (AEs) supervision on reducing treatment-related AEs in patients.@*METHODS@#66 NSCLC patients admitted to Shanghai Chest Hospital from July 2020 to October 2021 were prospectively collected. All the patients received 3 cycles of neoadjuvant treatment of Camrelizumab in combination with Docetaxel and Cisplatin. 4 weeks-6 weeks after neoadjuvant therapy, the patients accepted surgical treatment. One cycle of postoperative adjuvant treatment was given within 30 days after surgery, and 3 weeks after the completion of postoperative adjuvant treatment, Camrelizumab consolidation treatment was intiated, with a total of 13 cycles. The quality of life-C30 (QoL-C30) was used to measure patients' quality of life and the occurrence of AEs was monitored.@*RESULTS@#The overall safety is good, with a total of 300 AEs occurring in 66 patients, including 282 cases of grade 1-2 AEs and 18 cases of grades 3-4 AEs. The most common grades 3-4 AEs associated with PD-1 antibodies occurred in 6 cases (9.1%). Neoadjuvant therapy supervision can lead to a decrease in patients' QOL-C30 scores (P<0.05) and an improvement in their quality of life.@*CONCLUSIONS@#Camrelizumab combined with Docetaxel and Cisplatin can be used as a new adjuvant treatment for operable stage III NSCLC. Through the observation and control of AEs, treatment measures can be taken in time to reduce further complications, ensure patient' safety, and ensure the authenticity, scientificity and reliability of clinical trial data.

GPRC5B protects osteoarthritis by regulation of autophagy signaling

Osteoarthritis (OA) is one of the most common chronic diseases in the world. However, current treatment modalities mainly relieve pain and inhibit cartilage degradation, but do not promote cartilage regeneration. In this study, we show that G protein-coupled receptor class C group 5 member B (GPRC5B), an orphan G-protein-couple receptor, not only inhibits cartilage degradation, but also increases cartilage regeneration and thereby is protective against OA. We observed that Gprc5b deficient chondrocytes had an upregulation of cartilage catabolic gene expression, along with downregulation of anabolic genes in vitro. Furthermore, mice deficient in Gprc5b displayed a more severe OA phenotype in the destabilization of the medial meniscus (DMM) induced OA mouse model, with upregulation of cartilage catabolic factors and downregulation of anabolic factors, consistent with our in vitro findings. Overexpression of Gprc5b by lentiviral vectors alleviated the cartilage degeneration in DMM-induced OA mouse model by inhibiting cartilage degradation and promoting regeneration. We also assessed the molecular mechanisms downstream of Gprc5b that may mediate these observed effects and identify the role of protein kinase B (AKT)-mammalian target of rapamycin (mTOR)-autophagy signaling pathway. Thus, we demonstrate an integral role of GPRC5B in OA pathogenesis, and activation of GPRC5B has the potential in preventing the progression of OA.

Notch signaling pathway inhibitor DAPT improves alcohol-induced neuronal differentiation impairment in zebrafish / 南方医科大学学报

OBJECTIVE@#To explore the role of the Notch signaling pathway in regulating neuronal differentiation and sensorimotor ability in a zebrafish model of fetal alcohol spectrum disorder.@*METHODS@#Zebrafish embryos treated with DMSO or 50 μmol/L DAPT (a Notch signaling pathway inhibitor) were examined for mortality rate, hatching rate, malformation rate, and body length at 15 days post fertilization (dpf). The mRNA expression levels of sox2, neurogenin1 and huc in the treated zebrafish embryos were detected using in situ hybridization and qRT-PCR, and their behavioral responses to strong light and vibration stimulation were observed. The zebrafish embryos were then exposed to DMSO, 1.5% ethanol, DAPT, or both ethanol and DAPT, and the changes in mRNA expression levels of sox2, neurogenin1, huc, and the Notch signaling pathway genes as well as behavioral responses were evaluated.@*RESULTS@#Exposure to 50 μmol/L DAPT significantly increased the mortality rate of 1 dpf zebrafish embryos (P < 0.01), decreased the hatching rate of 2 dpf embryos (P < 0.01), increased the malformation rate of 3 dpf embryos (P < 0.001), and reduced the body length of 15 dpf embryos (P < 0.05). DAPT treatment significantly downregulated sox2 mRNA expression (P < 0.01) and increased neurogenin1 (P < 0.05) and huc (P < 0.01) mRNA expressions in zebrafish embryos. The zebrafish with DAPT treatment exhibited significantly shortened movement distance (P < 0.001) and lowered movement speed (P < 0.05) in response to all the stimulation conditions. Compared with treatment with 1.5% ethanol alone, which obviously upregulated notch1a, her8a and NICD mRNA expressions in zebrafish embryos (P < 0.05), the combined treatment with ethanol and DAPT significantly increased neurogenin1 and huc mRNA expression, decreased sox2 mRNA expression (P < 0.01), and increased the moving distance and moving speed of zebrafish embryos in response to strong light stimulation (P < 0.05).@*CONCLUSION@#Ethanol exposure causes upregulation of the Notch signaling pathway and impairs neuronal differentiation and sensorimotor ability of zebrafish embryos, and these detrimental effects can be lessened by inhibiting the Notch signaling pathway.